In the production of optically active D- or L-α-amino acids used as a raw material or intermediate, etc. in the field of pharmaceuticals, agriculture and fine chemistry, the amino acid having optical activity may be directly prepared as an optically active isomer with the desired optical activity or, it may be prepared as an optically active isomer having the desired optical activity by preparing a racemic mixture and then subjecting it to an optical resolution method.
In the process of producing D- or L-α-amino acids by an optical resolution of racemic amino acids, the remaining optical isomers after the optical resolution may usually be subjected to racemization process and then reused as racemic mixtures for an optical resolution for economic reasons.
Recently, L-amino acid or D-amino acid can be mass-produced by chemical methods or biological methods. In case where such mass-produced L-amino acid or D-amino acid is inexpensive but the L-amino acid or D-amino acid having an opposite steric structure is expensive, the racemization of amino acids may be an important key technology whereby an amino acid having an inexpensive steric structure is transformed to an amino acid having an expensive steric structure.
As a racemization method of α-amino acid having optical activity, several methods including chemical and biological methods have been disclosed.
U.S. Pat. Nos. 2,586,154 and 4,769,486 disclose a chemical racemization method wherein α-amino acid is introduced in a strong acid or alkaline aqueous solution and subjected to a racemization at a high temperature. In the methods of these documents, the severe reaction conditions (high temperature, long reaction period) may cause decomposition of α-amino acid and thus many side products are generated. [See Advances in Protein Chemistry, Vol. 4 , p. 4339 (1948)].
As an improved version of the above-described chemical method, U.S. Pat. No. 3,213,106 (1965) has proposed a racemization method wherein α-amino acid is introduced in a closed vessel and subjected to a racemization at a high temperature (100˜150° C.). The method has problems that the reaction temperature is very high above the boiling point of water and thus the reactor needs to be a closed vessel that can endure the high pressure.
As a further improved method of the above-described chemical method, U.S. Pat. No. 4,401,820 (1983) discloses a racemization method wherein the racemization is more easily carried out at a temperature of 100° C. or less by using organic acids such as formic acid, acetic acid, propionic acid instead of water as a solvent and employing a variety of aldehydes as a catalyst. However, there are problems that the organic acid used as a solvent has a bitter smell and toxicity and thus requires a complicated process for its use and recovery.
Japanese Patent Laid-Open Publications H11-228512 and H11-322684 (corresponding to European Patent Publication EP 0937705A) disclose a catalytic racemization method wherein a racemization of α-amino acid is carried out by using salicylaldehyde as a catalyst under an acidic condition. In the method of these documents, the yield of α-amino acid is low due to severe reaction conditions.
Meanwhile, it has been known that a Schiff base obtained by reacting salicylaldehyde or substituted salicylaldehyde with α-amino acid is combined with a copper ion (Cu2+) to give a copper metal complex (Cu-Metal Complex), which can be utilized as a very useful racemization catalyst (Scheme 1). [Bulletin of the Chemical Society of Japan, Vol 51 (8), 2366 (1978); Biochemistry, Vol 17 (16) 3183 (1978); Inorganic Chemistry, Vol 9 (9), 2104 (1970); Bulletin of the Chemical Society of Japan, Vol 42 (9), 2628 (1969); Australian Journal of Chemistry, Vol 19, 2143 (1966)].

The above Cu-metal complex is easy to prepare and is useful as a racemization catalyst since a variety of amino acids can be racemized at the normal temperature even with a small amount under a basic condition in a water solvent. However, the above Cu-metal complex has problems that, when the resultant reaction mixture is acidified in order to isolate racemic α-amino acid, the Cu-metal complex catalyst may be decomposed and thus cannot be recycled and that the salicylaldehyde and copper ion which result from decomposition should be removed during the separation and purification step of α-amino acid.